Dimers of the neuropeptide Y (NPY) Y2 receptor show asymmetry in agonist affinity and association with G proteins.
In conditions precluding activation of G proteins, the binding of agonists to dimers of the neuropeptide Y (NPY) Y2 receptor shows two components of similar size, but differing in affinity. The dimers of all NPY receptors are solubilized as approximately 180-kDa complexes containing one G protein alpha beta gamma trimer. These heteropentamers are stable to excess agonists, chelators, and alkylators. However, dispersion in the weak surfactant cholate releases approximately 300-kDa complexes. These findings indicate that both protomers in the Y2 dimer are associated with G protein heterotrimers, but the extent of interaction depends on affinity for the agonist peptide. The G protein in contact with the first-liganded, higher-affinity protomer should have a stronger interaction with the receptor and a larger probability of activation.
Parker
M S
MS
Department of Molecular Cell Sciences, University of Memphis, Memphis, Tennessee, USA. stevenleonardparker@msn.com
Sah
R
R
Balasubramaniam
A
A
Sallee
F R
FR
Sweatman
T
T
Park
E A
EA
Parker
S L
SL
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004963:Estrenes / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000819:agonists* / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006801:Humans; D051379:Mice; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D055503:Protein Multimerization; D011760:Pyrrolidinones / Q000494:pharmacology; D011817:Rabbits; D017476:Receptors, Neuropeptide Y / Q000737:chemistry / Q000378:metabolism*
D004963:Estrenes; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D019204:GTP-Binding Proteins